We propose the Sirius workstation, an innovative microscope system combining the capabilities of automated neuron reconstruction using guided image collection, cell electrophysiological recording, and cell filling in live tissue. Sirius will be the first commercially available system to a) enable direct recording of single distal synaptic connections formed between different areas, b) facilitate repeated monitoring of potential alterations in neuronal morphology during or as a result of stimulation, and c) permit simultaneous recording of one or more neurons formed between different areas in brain slices identified based on neuronal structure. This system will allow significant advancements in integrated studies of neural function and structure in basic neuroscience as well as in neurotoxicology and pharmacological research and development, representing clear progress beyond the state-of-the-art. PUBLIC HEALTH RELEVANCE The proposed project will enable new important studies in neuroscience research which are not currently feasible. A system that combines the capabilities of guided automated neuron reconstruction, cell electrophysiological recording and cell filling in live tissue will allow researchers to more accurately identify cells within a neural circuit, even those located at a distance from the original cell. The overall effect of this project will permit the collection of highly relevant data in integrated studies of neural function and structure in basic neuroscience, neurotoxicology, pharmacological research, and related fields involving research in neurological disease. [unreadable] [unreadable] [unreadable]